A small percentage of patients who receive lung transplantation develop a deadly increase of blood ammonia levels, according to a collaborative study by researchers at the University of Pennsylvania Medical Center and The Children's Hospital of Philadelphia.

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EMBARGOED FOR RELEASE -- February 14, 2000, 5 p.m. Eastern Standard Time Philadelphia, Pa. -- A small percentage of patients who receive lung transplantation develop a deadly increase of blood ammonia levels, according to a collaborative study by researchers at the University of Pennsylvania Medical Center and The Children's Hospital of Philadelphia. A report on the findings will appear in the February 15 issue of The Annals of Internal Medicine.

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The researchers studied 145 consecutive adult patients who received lung transplantation over a five-year period at the University of Pennsylvania Medical Center. Six of the 145 patients, or 4 percent, developed high levels of blood ammonia, called hyperammonemia. Of those six patients with hyperammonemia, four, or 67 percent, died within 30 days of the surgery, compared to deaths in 24 (or 17 percent) of the 139 patients with normal levels of blood ammonia. A fifth patient with hyperammonemia died 34 days after the surgery. In all five cases, death was preceded by coma and increased pressure in the brain.

The only lung transplant patient with hyperammonemia who survived had her condition recognized early and received hemodialysis and medications to lower her blood ammonia level. "This one case does not prove that this therapy will benefit all patients with this post-transplant complication, but it does suggest a useful area for further study," said Gerard T. Berry, M.D., an endocrinologist and geneticist at The Children's Hospital of Philadelphia and senior author of the study.

The number of lung transplantations nationwide increased rapidly during the 1990s, for conditions such as emphysema, cystic fibrosis and other pulmonary diseases. Among the lung transplant recipients in the study sample who developed hyperammonemia, the researchers identified certain risk factors: major gastrointestinal complications (such as intestinal bleeding, intestinal perforation or infection), the need for feeding through an intravenous line (total parenteral nutrition), and high pressure in the arteries leading to the lungs (primary pulmonary hypertension). Another possible risk factor is deficiency in a liver enzyme, called glutamine synthetase, which plays a role in ammonia metabolism.

"Further studies are needed to characterize the causes and possible treatments of hyperammonemia after lung transplantation," said Gary R. Lichtenstein, M.D., a member of the Gastroenterology Division of the Department of Medicine and Director of the Inflammatory Bowel Disease Center at the Hospital of the University of Pennsylvania, and lead author of the paper. "In the meantime, physicians need to be aware of this potential complication of lung transplantation."

The Children's Hospital of Philadelphia, the nation's first children's hospital, is a leader in patient care, education and research. This 373-bed multispecialty hospital provides comprehensive pediatric services, including home care, to children from before birth through age 19. The hospital is second in the United States among all children's hospitals in total research funding from the National Institutes of Health. The University of Pennsylvania Medical Center's sponsored research and training ranks second in the United States based on grant support from the National Institutes of Health, the primary funder of biomedical research and training in the nation -- $238 million in federal fiscal year 1999.

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